Sodium Current and Arrhythmogenesis in Heart Failure

Santana, Luis Fernando; Núñez‐Durán, Harol; Dilly, Keith W.; Lederer, W. Jonathan

doi:10.1016/j.hfc.2005.06.003

Cited by 6 publications

(2 citation statements)

References 55 publications

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“…28,35,36) The corresponding reduction in sodium pump activity leads to increased intracellular Na + -concentrations, which enhances Ca 2+ -accumulation via the exchanger. 37,38,39) This effect is supported by the prolonged action potential of failing human cardiomyocytes (1038 ms versus 649 ms).…”

Section: +mentioning

confidence: 93%

Increased Functional Importance of the Na,Ca-Exchanger in Contracting Failing Human Myocardium but Unchanged Activity in Isolated Vesicles

et al. 2007

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SUMMARYThe present study aimed to investigate the hypothesis that the function of the Na,Caexchanger (NCX) is of higher importance for contractility and Ca 2+-homeostasis in left ventricle from terminally failing than from nonfailing human hearts.The effect of decreasing extracellular [Na] e (140 to 25 mmol/L) on force of contraction in isolated left ventricular papillary muscle strips was studied as a reflection of NCX function in multicellular preparations (terminally failing, DCM, dilated cardiomyopathy, NYHA IV, n = 13; nonfailing, NF, donor hearts, n = 10). Decreasing [Na] e has previously been shown to increase contractility in vitro secondary to a decreased Ca 2+ -extrusion by the NCX. In addition, the NCX activity was measured as Na + -dependent 45 Ca 2+ -uptake into isolated myocardial vesicles as a function of time and Ca 2+ -concentration (DCM n = 8, NF n = 8). Decreasing [Na] e enhanced the contractility of papillary muscle strips in both DCM and NF, but the contractility of DCM was increased at smaller reductions of [Na] e than NF. The NCX activity in isolated myocardial vesicles was unchanged as a function of time (T 1/2 : DCM 2.4 ± 0.3 s versus NF 2.5 ± 0.3 s) and as a function of Ca These results demonstrate a higher sensitivity of the failing human myocardium towards Na,Ca-exchanger mediated positive inotropic effects, suggesting a higher significance of the Na,Ca-exchanger for the extrusion of Ca 2+ -ions in intact failing versus nonfailing human myocardium. Since the activity and the Ca 2+ -affinity of the Na,Caexchanger in isolated vesicles was unchanged, we propose that alterations in Ca 2+ -and Na + -homeostasis (due to impaired function of the sarcoplasmic reticulum and the Na + , K + -ATPase) or the prolonged action potential are the reason for this observation. (Int Heart J 2007; 48: 755-766)

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Section: +mentioning

confidence: 93%

Increased Functional Importance of the Na,Ca-Exchanger in Contracting Failing Human Myocardium but Unchanged Activity in Isolated Vesicles

et al. 2007

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“…The treatment strategy in CAST involved simply suppressing focal activity and blocking the sodium channel. Later, it was found that sodium channels are down-regulated in patients with heart failure (Santana et al, 2005), and therefore further blockade of those channels may promote arrhythmia.…”

Section: Limitations Of Current Therapiesmentioning

confidence: 99%

Reactive oxygen species-targeted therapeutic interventions for atrial fibrillation

Sovari¹,

Dudley²

2012

Front. Physio.

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Atrial fibrillation (AF) is the most common arrhythmia that requires medical attention, and its incidence is increasing. Current ion channel blockade therapies and catheter ablation have significant limitations in treatment of AF, mainly because they do not address the underlying pathophysiology of the disease. Oxidative stress has been implicated as a major underlying pathology that promotes AF; however, conventional antioxidants have not shown impressive therapeutic effects. A more careful design of antioxidant therapies and better selection of patients likely are required to treat effectively AF with antioxidant agents. Current evidence suggest inhibition of prominent cardiac sources of reactive oxygen species (ROS) such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and targeting subcellular compartments with the highest levels of ROS may prove to be effective therapies for AF. Increased serum markers of oxidative stress may be an important guide in selecting the AF patients who will most likely respond to antioxidant therapy.

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Electrophysiological Mechanisms of Cardiac Arrhythmias

Issa¹

2009

Clinical Arrhythmology and Electrophysiology

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Sodium Current and Arrhythmogenesis in Heart Failure

Cited by 6 publications

References 55 publications

Increased Functional Importance of the Na,Ca-Exchanger in Contracting Failing Human Myocardium but Unchanged Activity in Isolated Vesicles

Increased Functional Importance of the Na,Ca-Exchanger in Contracting Failing Human Myocardium but Unchanged Activity in Isolated Vesicles

Reactive oxygen species-targeted therapeutic interventions for atrial fibrillation

Electrophysiological Mechanisms of Cardiac Arrhythmias

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